Abstract
DNA polymerases sometimes stall during DNA replication at sites where DNA is damaged, or upon encounter with proteins or secondary structures of DNA. When that happens, the polymerase clamp PCNA can become modified with a single ubiquitin moiety at lysine 164, opening DNA Damage Tolerance (DDT) mechanisms that either repair or bypass the lesions. An alternative repair mechanism is the salvage recombination (SR) pathway, which copies information from the sister chromatid. SUMOylation of PCNA at the same lysine, or at lysine 127, can recruit the Srs2 helicase, which negatively controls SR. Recently, we have dissected the relationship between SR and the DDT pathways, and showed that overexpression of either the PCNA unloader Elg1, or the Rad52 homologous recombination protein, can bypass the repression by Srs2. Our results shed light on the interactions between different DNA damage repair/bypass proteins, and underscore the importance of PCNA modifications in organizing the complex task of dealing with DNA damage during replication of the genetic material.
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Acknowledgements
We thank past and present members of the Kupiec lab for support, ideas and support. This work was supported by grants from the Israel Science Foundation, the Minerva Center and the Israel Cancer Research Fund to MK.
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Communicated by Judith Berman.
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Arbel, M., Liefshitz, B. & Kupiec, M. How yeast cells deal with stalled replication forks. Curr Genet 66, 911–915 (2020). https://doi.org/10.1007/s00294-020-01082-y
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DOI: https://doi.org/10.1007/s00294-020-01082-y